冠状动脉造影术后接受降低同型半胱氨酸的B族维生素治疗的患者的死亡率和心血管事件：一项随机对照试验。

Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial.

作者信息

Ebbing Marta, Bleie Øyvind, Ueland Per Magne, Nordrehaug Jan Erik, Nilsen Dennis W, Vollset Stein Emil, Refsum Helga, Pedersen Eva Kristine Ringdal, Nygård Ottar

机构信息

Department of Heart Disease, Haukeland University Hospital, Jonas Liesvei 65, 5021 Bergen, Norway.

出版信息

JAMA. 2008 Aug 20;300(7):795-804. doi: 10.1001/jama.300.7.795.

DOI:10.1001/jama.300.7.795

PMID:18714059

Abstract

CONTEXT

Observational studies have reported associations between circulating total homocysteine concentration and risk of cardiovascular disease. Oral administration of folic acid and vitamin B(12) can lower plasma total homocysteine levels.

OBJECTIVE

To assess the effect of treatment with folic acid and vitamin B(12) and the effect of treatment with vitamin B(6) as secondary prevention in patients with coronary artery disease or aortic valve stenosis.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind controlled trial conducted in the 2 university hospitals in western Norway in 1999-2006. A total of 3096 adult participants undergoing coronary angiography (20.5% female; mean age, 61.7 years) were randomized. At baseline, 59.3% had double- or triple-vessel disease, 83.7% had stable angina pectoris, and 14.9% had acute coronary syndromes.

INTERVENTIONS

Using a 2 x 2 factorial design, participants were randomly assigned to 1 of 4 groups receiving daily oral treatment with folic acid, 0.8 mg, plus vitamin B(12), 0.4 mg, plus vitamin B(6), 40 mg (n = 772); folic acid plus vitamin B(12) (n = 772); vitamin B(6) alone (n = 772); or placebo (n = 780).

MAIN OUTCOME MEASURES

The primary end point was a composite of all-cause death, nonfatal acute myocardial infarction, acute hospitalization for unstable angina pectoris, and nonfatal thromboembolic stroke.

RESULTS

Mean plasma total homocysteine concentration was reduced by 30% after 1 year of treatment in the groups receiving folic acid and vitamin B(12). The trial was terminated early because of concern among participants due to preliminary results from a contemporaneous Norwegian trial suggesting adverse effects from the intervention. During a median 38 months of follow-up, the primary end point was experienced by a total of 422 participants (13.7%): 219 participants (14.2%) receiving folic acid/vitamin B(12) vs 203 (13.1%) not receiving such treatment (hazard ratio, 1.09; 95% confidence interval, 0.90-1.32; P = .36) and 200 participants (13.0%) receiving vitamin B(6) vs 222 (14.3%) not receiving vitamin B(6) (hazard ratio, 0.90; 95% confidence interval, 0.74-1.09; P = .28).

CONCLUSIONS

This trial did not find an effect of treatment with folic acid/vitamin B(12) or vitamin B(6) on total mortality or cardiovascular events. Our findings do not support the use of B vitamins as secondary prevention in patients with coronary artery disease.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT00354081.

摘要

背景

观察性研究报告了循环总同型半胱氨酸浓度与心血管疾病风险之间的关联。口服叶酸和维生素B12可降低血浆总同型半胱氨酸水平。

目的

评估叶酸和维生素B12治疗以及维生素B6作为冠状动脉疾病或主动脉瓣狭窄患者二级预防的治疗效果。

设计、地点和参与者：1999年至2006年在挪威西部的2所大学医院进行的随机、双盲对照试验。共有3096名接受冠状动脉造影的成年参与者（20.5%为女性；平均年龄61.7岁）被随机分组。基线时，59.3%患有双支或三支血管病变，83.7%患有稳定型心绞痛，14.9%患有急性冠状动脉综合征。

干预措施

采用2×2析因设计，参与者被随机分配到4组中的1组，分别接受每日口服叶酸0.8毫克加维生素B12 0.4毫克加维生素B6 40毫克（n = 772）；叶酸加维生素B12（n = 772）；单独使用维生素B6（n = 772）；或安慰剂（n = 780）。

主要结局指标

主要终点是全因死亡、非致命性急性心肌梗死、不稳定型心绞痛急性住院和非致命性血栓栓塞性卒中的复合终点。

结果

接受叶酸和维生素B12治疗的组在治疗1年后血浆总同型半胱氨酸浓度平均降低了30%。由于同期挪威一项试验的初步结果表明干预存在不良反应，参与者对此表示担忧，该试验提前终止。在中位38个月的随访期间，共有422名参与者（13.7%）达到主要终点：219名（14.2%）接受叶酸/维生素B12治疗的参与者与203名（13.1%）未接受此类治疗的参与者（风险比，1.09；95%置信区间，0.90 - 1.32；P = 0.36），以及200名（13.0%）接受维生素B6治疗的参与者与222名（14.3%）未接受维生素B6治疗的参与者（风险比，0.90；95%置信区间，0.74 - 1.09；P = 0.28）。